Category: Methodology

Dream of the Magic Buckshot

Paul Ehrlich in the early 1900s sought a “magic bullet” for each disease (including cancer). Given the alternatives at the time, when he found Salvarsan it could be considered a magic bullet against syphilis. Today Dr. Dale Bredesen has replaced “magic” with “silver” and “bullet” with “buckshot.” In his effort to cure Alzheimer’s “Bredesen believed in firing a “silver buckshot” (a reference to the sprayed pellets that come out of shotgun shells) by modifying 36 factors simultaneously” (Gellman, p. 18).

I have not investigated Dr. Bredesen’s “cure” for Alzheimer’s and express no opinion on it. I will express the opinion that I do not like the arrogantly dismissive tone of Lindsay Gellman’sThe New York Times article, bowing to “experts,” but calling Bredesen “Mr.” instead of the “Dr.” he has earned.

And I do like the idea that sometimes what is effective against a disease (including cancer) is not a single drug or therapy, but several taken together. For example, multi-drug cocktails have been effectively used against HIV, childhood leukemia, and Hodgkin’s lymphoma.

Ehrlich’s big dream was to find a magic bullet for each disease. But maybe it is mostly more promising to dream of the magic buckshot.

[N.B., the “Paul Ehrlich” I refer to is not the contemporary environmental alarmist “Paul Ehrlich” who famously lost his bet with the heroic heretic Julian Simon.]

The NYT article quoted above:

Lindsay Gellman. “Lifestyle to Reverse Alzheimer’s Carries High Costs and, Many Say, False Hope.” The New York Times, First Section (Sun., May 25, 2025): 1 & 18.

(Note: the online version of the NYT article was updated May 31, 2025, and has the title “An Expensive Alzheimer’s Lifestyle Plan Offers False Hope, Experts Say.”)

How Did Ed Smylie and His Team Create the Kludge That Saved the Crew of Apollo 13?

Gary Klein in Seeing What Others Don’t analyzed cases of innovation, and sought their sources. One source he came up with was necessity. His compelling example was the firefighter Wag Dodge who, with maybe 60 seconds until he would be engulfed in flame, lit a match to the grass around him, and then laid down in the still-hot embers. The roaring fire bypassed the patch he pre-burned, and his life was saved. The story is well-told in Norman Maclean’s Young Men and Fire.

Pondering more cases of necessity might be useful to help us understand, and encourage, future innovation. One candidate might be the kludge that Ed Smylie and his engineers put together to save the Apollo 13 crew from suffocating after an explosion blew up their command capsule oxygen tank.

Necessity may be part of it, but cannot be the whole story. Humanity needed to fly for thousands of years, but it took Wilbur Wright to make it happen. (This point is made in Kevin Ashton’s fine and fun How to Fly a Horse.)

I have ordered the book co-authored by Lovell, and mentioned in a passage quoted below, in case it contains insight on how the Apollo 13 kludge was devised.

(p. B11) Ed Smylie, the NASA official who led a team of engineers that cobbled together an apparatus made of cardboard, plastic bags and duct tape that saved the Apollo 13 crew in 1970 after an explosion crippled the spacecraft as it sped toward the moon, died on April 21 [2025] in Crossville, Tenn. He was 95.

. . .

Soft-spoken, with an accent that revealed his Mississippi upbringing, Mr. Smylie was relaxing at home in Houston on the evening of April 13 when Mr. Lovell radioed mission control with his famous (and frequently misquoted) line: “Uh, Houston, we’ve had a problem.”

An oxygen tank had exploded, crippling the spacecraft’s command module.

Mr. Smylie, . . ., saw the news on television and called the crew systems office, according to the 1994 book “Lost Moon,” by Mr. Lovell and the journalist Jeffrey Kluger. The desk operator said the astronauts were retreating to the lunar excursion module, which was supposed to shuttle two crew members to the moon.

“I’m coming in,” Mr. Smylie said.

Mr. Smylie knew there was a problem with this plan: The lunar module was equipped to safely handle air flow for only two astronauts. Three humans would generate lethal levels of carbon dioxide.

To survive, the astronauts would somehow need to refresh the canisters of lithium hydroxide that would absorb the poisonous gases in the lunar excursion module. There were extra canisters in the command module, but they were square; the lunar module ones were round.

“You can’t put a square peg in a round hole, and that’s what we had,” Mr. Smylie said in the documentary “XIII” (2021).

He and about 60 other engineers had less than two days to invent a solution using materials already onboard the spacecraft.

. . .

In reality, the engineers printed a supply list of the equipment that was onboard. Their ingenious solution: an adapter made of two lithium hydroxide canisters from the command module, plastic bags used for garments, cardboard from the cover of the flight plan, a spacesuit hose and a roll of gray duct tape.

“If you’re a Southern boy, if it moves and it’s not supposed to, you use duct tape,” Mr. Smylie said in the documentary. “That’s where we were. We had duct tape, and we had to tape it in a way that we could hook the environmental control system hose to the command module canister.”

Mission control commanders provided step-by-step instructions to the astronauts for locating materials and building the adapter.

. . .

The adapter worked. The astronauts were able to breathe safely in the lunar module for two days as they awaited the appropriate trajectory to fly the hobbled command module home.

. . .

Mr. Smylie always played down his ingenuity and his role in saving the Apollo 13 crew.

“It was pretty straightforward, even though we got a lot of publicity for it and Nixon even mentioned our names,” he said in the oral history. “I said a mechanical engineering sophomore in college could have come up with it.”

For the full obituary, see:

Michael S. Rosenwald. “Ed Smylie Dies at 95; His Team of Engineers Saved Apollo 13 Crew.” The New York Times (Tuesday, May 20, 2025): B11.

(Note: ellipses, and bracketed year, added.)

(Note: the online version of the obituary was updated May 18, 2025, and has the title “Ed Smylie, Who Saved the Apollo 13 Crew With Duct Tape, Dies at 95.”)

Klein’s book that I praise in my introductory comments is:

Klein, Gary A. Seeing What Others Don’t: The Remarkable Ways We Gain Insights. Philadelphia, PA: PublicAffairs, 2013.

Maclean’s book that I praise in my introductory comments is:

Maclean, Norman. Young Men and Fire. new ed., Chicago: University of Chicago Press, 2017.

Ashton’s book that I praise in my introductory comments is:

Ashton, Kevin. How to Fly a Horse: The Secret History of Creation, Invention, and Discovery. New York: Doubleday, 2015.

The book co-authored by Lovell and mentioned above is:

Lovell, Jim, and Jeffrey Kluger. Lost Moon: The Perilous Voyage of Apollo 13. Boston, MA: Houghton Mifflin, 1994.

The Chicago School of Economics Was Once Uniquely Focused on Real World Problems

The Chicago School of Economics, most associated with Milton Friedman and George Stigler, saw itself as different from all the other top graduate programs in economics. At Chicago, the priority was solving applied problems, and only as much mathematics and theory should be used as was necessary to solve them. The other schools prioritized mathematical puzzle-solving and mathematical rigor and sophistication.

For those who might suspect Chicago was full of itself, the non-Chicago economists Arjo Klamar and David Colander dispelled the suspicion in their The Making of an Economist. After thorough interviewing and surveying of graduate students at the five or six top graduate programs, they concluded that graduate students at all but Chicago were cynically discouraged to realize that they were being trained to solve mathematical puzzles, while only those at Chicago still felt that they were being trained to matter in the real world.

I noticed that a recent obituary for the economist Stanley Fischer quotes Fischer as stating some diplomatic confirmation of the Klamar and Colander conclusion:

After earning his Ph.D. at M.I.T. in 1969, Mr. Fischer moved to the University of Chicago as a postdoctoral researcher and assistant professor. “At M.I.T. you did the mathematical work,” he told The New York Times in 1998, “and at Chicago you asked the question of how this applies to the real world” (Hagerty 2025, p. A17).

Alas, I fear that what was once true, is true no longer. I fear that if Klamar and Colander were to repeat their study today, they would find that Chicago has joined the other top programs in prioritizing mathematical puzzle-solving and mathematical rigor and sophistication.

The obituary of Stanley Fischer, quoted above, is:

James R. Hagerty. “Stanley Fischer, 81, Economist Who Helped Defuse Crises, Dies.” The New York Times (Mon., June 2, 2025): A17.

(Note: the online version of the Steve Lohr article was updated June 10, 2025, and has the title “Stanley Fischer, Who Helped Defuse Financial Crises, Dies at 81.”)

The Klamar and Colander book mentioned above is:

Klamer, Arjo, and David Colander. The Making of an Economist. Boulder, CO: Westview Press, 1990.

“Gold Standard” RCT Studies Do Not Always Agree on Broad Issues

Randomized double-blind clinical trials (RCTs) are usually labeled the “gold standard” of medical evidence. But any given clinical trial can be done in an infinite number of ways. The length and duration of the RCT can vary. The eligibility requirements can vary. The definition of the placebo or comparison treatment can vary.

So on the broad issue of whether red meat is good for the heart, an RCT that compares the heart effects of red meat versus the heart effects of chicken, can yield different results than an RCT that compares the heart effects of red meat versus the heart effects of a plant-based diet.

Both RCTs might be competently done, involving no dishonesty or fraud.

We tend to overgeneralize the results of an RCT, for instance saying “red meat is heart healthy,” or “red meat is not heart healthy.” Whereas all we are justified in saying is “red meat is equally heart healthy as chicken” and “read meat is less heart healthy than a plant-based diet.”

Since RCTs are expensive and time-consuming, physicians and patients will often have to choose between treatments where no RCT has been done where the researchers made the choices that are most relevant to the patient’s situation.

And in an environment where RCT costs are high and funding is scarce, are researchers to be condemned if among the myriad varying ways of setting up the RCT, they choose the ways most likely to yield the results that will be appealing to their funder?

The article quoted below, in passages I did not quote, assumes this is only an issue with industry-funded research. But government funding review panels also have preferred outcomes. For example, Charles Piller in Doctored has recently documented that government funders have been more likely to fund RCTs that support the amyloid hypothesis of the cause of Alzheimer’s.

So is there hope for those who want to take effective action against dire disease? Yes, we can recognize that not all sound actionable evidence comes from RCTs. We can stop mandating Phase 3 trials, so that a more diverse assortment of plausible therapies can be explored. We can encourage diverse, decentralized funding sources.

(p. D6) In a review published last week in the American Journal of Clinical Nutrition, scientists came to a concerning conclusion. Red meat appeared healthier in studies that were funded by the red meat industry.

. . .

Past research funded by the sugar industry, for instance, has downplayed the relationship between sugar and health conditions like obesity and heart disease. And studies funded by the alcohol industry have suggested that moderate drinking could be part of a healthy diet.

Miguel López Moreno, a researcher at Francisco de Vitoria University in Spain who led the new analysis, said in an email that he wanted to know if similar issues were happening with the research on unprocessed red meat.

. . .

Dr. Moreno and his colleagues found that the trials with funding from the red meat industry were nearly four times as likely to report favorable or neutral cardiovascular results after eating unprocessed red meat when compared with the studies with no such links.

. . .

These differing results may have stemmed from how the studies were set up in the first place, Dr. Tobias wrote in an editorial for the American Journal of Clinical Nutrition that accompanied the new study.

Individual nutrition studies can be good at showing how the health effects of certain foods compare with those of other specific foods. But to demonstrate whether a particular food, or food group like red meat, is good or bad for health in general, scientists must look at the results from many different studies that compare it to all possible food groups and diets.

The new review showed that, on the whole, the industry-funded red meat studies neglected to compare red meat to the full range of foods people might eat — including food we know to be good for the heart like whole grains or plant-based protein sources such as tofu, nuts or legumes. Instead, many of the studies compared unprocessed red meat to other types of animal protein like chicken or fish, or to carbohydrates like bagels, pasta or rice.

The independently funded studies, on the other hand, compared red meat to “the full spectrum” of different diets — including other types of meat, whole grains and heart-healthy plant foods like soy products, nuts and beans — Dr. Tobias said. This more comprehensive look offers a fuller picture of red meat’s risks or benefits, she said.

. . .

A spokeswoman for the National Cattlemen’s Beef Association said in an email that “beef farmers and ranchers support gold standard scientific research,” and that both animal and plant sources of protein can be part of a heart-healthy diet.

For the full story see:

Caroline Hopkins Legaspi. “Eyes on the Outcomes Of Red Meat Research.” The New York Times (Tues., May 27, 2025): D6.

(Note: ellipses added.)

(Note: the online version of the story has the date May 20, 2025, and has the title “Is Red Meat Bad for Your Heart? It May Depend on Who Funded the Study.”)

The academic article co-authored by Moreno and mentioned above is:

López-Moreno, Miguel, Ujué Fresán, Carlos Marchena-Giráldez, Gabriele Bertotti, and Alberto Roldán-Ruiz. “Industry Study Sponsorship and Conflicts of Interest on the Effect of Unprocessed Red Meat on Cardiovascular Disease Risk: A Systematic Review of Clinical Trials.” The American Journal of Clinical Nutrition 121, no. 6 (June 2025): 1246-57.

Some other articles discussing cases where industry funding is alleged to have funded biased research are:

Anahad O’Connor. “Sugar Backers Paid to Shift Blame to Fat.” The New York Times (Tues., Sept. 13, 2016): A1 & ?.

(Note: the online version of the story has the date Sept. 12, 2016, and has the title “How the Sugar Industry Shifted Blame to Fat.”)

Alice Callahan. “Is Fake Meat Superior to the Real Thing?” The New York Times (Tues., Feb. 18, 2025): D7.

(Note: the online version of the story has the date Feb. 17, 2025, and has the title “Is Fake Meat Better for You Than Real Meat?”)

Roni Caryn Rabin. “U.S. Wooed Alcohol Industry for a Drinking Study.” The New York Times, First Section (Sun., March 18, 2018): 1 & ??.

(Note: the online version of the story has the date March 17, 2018, and has the title “Federal Agency Courted Alcohol Industry to Fund Study on Benefits of Moderate Drinking.”)

During the Pandemic “Experts” Suppressed the Open Continual Inquiry That Is Science

The governmental violation of the basic rights of citizens, especially the right of free speech, is the most painful and lasting legacy of the Covid-19 pandemic. To flourish in the future, it is worth our time to remember what happened and defend those who protected free speech and the pursuit of true science, which is a method of continual inquiry, not a body of fixed beliefs.

(p. C7) “Science,” the great theoretical physicist Richard Feynman wrote, “is the belief in the ignorance of experts.” The incorrigibly curious Feynman knew that skepticism and a willingness to assimilate new evidence propel the scientific endeavor. Yet by 2020, in response to a global pandemic, the dominant part of America’s political and media class had turned the imperative to “follow the science” into an expression of almost religious reverence for the judgment of experts. Many educated and otherwise intelligent Americans, meanwhile, made a single, bespectacled government scientist their idol: “In Fauci We Trust” read their lawn signs and bumper stickers.

Their faith was misplaced. Credentialed experts, especially those in the fields of epidemiology and public health, had tied themselves to badly flawed theories, closed their minds to new evidence and thrown the mantle of “science” over value judgments for which they had no special competence.

“An Abundance of Caution,” by the journalist David Zweig, documents the poor evidentiary basis for the prolonged school closures and attendant follies such as masking requirements and social distancing. Mr. Zweig distinguished himself throughout the pandemic by his willingness to question the assumptions of self-identified “Covid hawks.” When he dug into the epidemiological modeling papers whose projections seemed decisively to rule out the safety of opening schools, he found “a never-ending matryoshka doll” of citations, resting ultimately on an assumption conceded to be “arbitrary” by its initial author.

Mr. Zweig shows how evidence emerged early on—in March 2020—that the virus did not pose a serious threat to children. American public-health professionals remained largely impervious to this fact.

. . .

“In Covid’s Wake,” by the Princeton political scientists Frances Lee and Stephen Macedo, mostly remains within the idiom of polite academic prose, but they state with disarming plainness that “elite institutions failed us” by giving in to panic. Ms. Lee and Mr. Macedo marvel at how consensus plans—none of which would have required extended lockdowns—were thrown out before Americans ever began dying, in part because public-health experts were entranced by China’s harsh restrictions. American policymakers had sound advice ready at hand, but most of them took the view that safety outweighed individual liberties, economic activity and quality of life.

Where Mr. Zweig emphasizes incuriosity, Ms. Lee and Mr. Macedo stress the willful suppression of reasonable debate, including the unfortunate tendency to paint critics of lockdowns and mask mandates as racists, quacks and conspiracy theorists. Such conduct was especially evident on the question of Covid-19’s origins, as top scientists vilified anyone suggesting the virus may have leaked from a lab in Wuhan, China. Credulous journalists, academics and other cultural arbiters, the authors remind us, embraced the effective censorship of those who questioned the official line.

. . .

Ms. Lee and Mr. Macedo catalog reams of data to show that, before the availability of vaccines, areas imposing the severest restrictions earned no discernible health benefits.

. . .

(p. C8) In 2024 the U.S. House’s Select Subcommittee on the Coronavirus Pandemic issued a genuinely impressive 500-page report, covering Covid-19’s origins, the fraud in pandemic-response programs and the effectiveness or otherwise of various interventions.

For the full review see:

Philip Wallach. “Failing the Pandemic Test.” The Wall Street Journal (Wednesday, April 19, 2025): C7-C8.

(Note: ellipses added.)

(Note: the online version of the review has the date April 18, 2025, and has the title “‘An Abundance of Caution’ and ‘In Covid’s Wake’: Failing the Pandemic Test.”)

The books under review are:

Macedo, Stephen, and Frances Lee. In Covid’s Wake: How Our Politics Failed Us. Princeton, NJ: Princeton University Press, 2025.

Zweig, David. An Abundance of Caution: American Schools, the Virus, and a Story of Bad Decisions. Cambridge, MA: The MIT Press, 2025.

The over-500-page 2024 report issued by the House’s Select Subcommittee on the Coronavirus Pandemic, and praised above, is:

Pandemic, Select Subcommittee on the Coronavirus. “After Action Review of the Covid-19 Pandemic: The Lessons Learned and a Path Forward.” U.S. House of Representatives. Washington, D.C., Dec. 4, 2024.

Development of IVF Took 10 Years of Trial and Error

If the Joy television movie accurately reflects the history of the development of IVF (in vitro fertilization) then it illustrates a couple of themes that are important. One is the frequent fruitfulness of trial-and-error experimentation. The other is that some medical entrepreneurs are motivated by having some form of ‘skin-in-the-game,’ in this case nurse Jean Purdy. (Support for the second theme is more speculative than for the first, since the evidence that the real Jane Purdy experienced endometriosis and infertility is circumstantial.)

(p. A10) “Joy,” . . . begins in 1968 and charts the 10-year journey of trial, error and more trial and error by an odd trio of pioneers: Bob Edwards (James Norton), a biologist and true-believer in the possibilities of IVF; Patrick Steptoe (Bill Nighy), a surgical obstetrician who is less than convinced but can be; and Jean Purdy (Thomasin McKenzie), a nurse who signs on as Bob’s assistant and, as we learn, has her own agenda regarding infertile women. (Edwards received the 2010 Nobel Prize in Medicine, his partners having passed away.)

Jack Thorne’s screenplay massages the IVF medical story into a personal one, mostly about Jean, who is portrayed as a critical member of the team and the one whose life reflects the social uproar over the mission—giving childless women a choice about becoming mothers.

For the full television review see:

John Anderson. “The Birth of a Medical Miracle.” The Wall Street Journal (Monday, Nov 22, 2024): A10.

(Note: ellipsis added.)

(Note: the online version of the television review has the date November 21, 2024, and has the title “‘Joy’ Review: The Birth of a Medical Miracle on Netflix.”)

A Few More Months of Life Is Front Page News for Pancreatic Cancer Patients

For those with late stage pancreatic cancer, half live less than a year and half live longer than a year, according to the front page WSJ article quoted below. But the article seems to be celebrating a patient who has survived 17 months on a new drug. The patient has a feeling, perhaps because of a lesion that they radiated, that the drug may stop working soon.

So let’s say that without the drug she might have expected roughly a year of life, and now with the drug she has gotten roughly 17 months of life. Sure 17 months is better than 12 months.

But are our expectations so low and our cancer progress so slow, that an extra five months of life is front-page news?

(p. A1) Pranathi Perati was running out of time to treat her stage-four pancreatic cancer when she found out she would get another shot: a clinical trial testing a new experimental drug.

Perati’s odds were slim—3% of late-stage pancreatic-cancer patients are still alive after five years. And half of all pancreatic-cancer patients live for less than a year after their diagnosis. For Perati, the drug, daraxonrasib from Revolution Medicines, has helped keep her alive for 17 months and counting.

. . .

(p. A4) The pill has given her some fatigue and mouth ulcers, but she feels better than she did with chemo. A lesion in her lung started progressing this past winter and was radiated, but her disease has been stable otherwise.

“Seventeen months is a lot of good time to buy,” she said. Still, Perati worries that her time on the drug might soon run out. She has started looking for more options. Her son is set to graduate high school this summer.

For the full story see:

Brianna Abbott. “Treatments Offer Hope On Pancreatic Cancer.” The Wall Street Journal (Saturday, March 1, 2025): A1 & A4.

(Note: ellipsis added.)

(Note: the online version of the story has the date February 28, 2025, and has the title “New Treatments Give Hope to Patients With One of the Deadliest Cancers.”)

It May Take a “Thorny Character” to Be “Willing to Challenge Entire Establishment Belief Systems”

The obituary quoted below misidentifies Richard Bernstein’s main contribution. Yes, it is noteworthy that he was probably the first diabetes sufferer to effectively and continually monitor his own blood glucose level. But his main contribution was that by careful self-monitoring and trial-and-error experimentation he discovered that his health improved when he cutback on both carbs and insulin.

The obituary writer quotes Gary Taubes, but either didn’t read his book or disagrees with it, because Taubes is clear about Bernstein’s main contribution.

I am halfway through Taubes’s book. It is long and sometimes deep in the weeds, but comes highly recommended by Marty Makary and Siddhartha Mukherjee, both of whom I highly respect. The book sadly highlights how mainstream medicine can be very slow to reform clinical practice to new knowledge.

(p. C6) Richard Bernstein was flipping through a medical trade journal in 1969 when he saw an advertisement for a device that could check blood-sugar levels in one minute with one drop of blood. It was marketed to hospitals, not consumers, but Bernstein wanted one for himself. He had been sick his entire life and was worried he was running out of time.

. . .

Since he wasn’t a doctor, the manufacturer wouldn’t even sell him a device. So, he bought one under the name of his wife, Dr. Anne Bernstein, a psychiatrist.

He experimented with different doses of insulin and the frequency of shots. He eased off carbohydrates. He checked his blood sugar constantly to see how it was reacting.

After experimenting for several years, he figured out that if he maintained a low-carb diet, he didn’t need as much insulin and could avoid many of the wild swings in his blood-sugar levels. By checking his blood sugar throughout the day, he learned how to maintain normal levels. It changed his life.

. . .

With his diabetes under control, he tried to spread the word and change the way the disease is treated. In the early years, he was dismissed by much of the medical establishment. His ideas went against accepted wisdom and he was, after all, not a doctor. In 1979, at the age of 45, he enrolled at the Albert Einstein College of Medicine, where he received his M.D.

“I never wanted to be a doctor,” he told the New York Times in 1988. “But I had to become one to gain credibility.”

Bernstein went into private practice in Mamaroneck, N.Y., where he treated diabetics and continued to advocate for his ideas—to his patients, in articles, YouTube videos, letters to the editor, and writing books, including “Dr. Bernstein’s Diabetes Solution.”

. . .

Gary Taubes, the author of “Rethinking Diabetes,” said that it was Bernstein’s work that eventually led to the Diabetes Control and Complications Trial, a landmark study that demonstrated that diabetics could blunt the destructive effects of the disease by keeping their blood-sugar levels nearer normal. Released in 1993, the results led to the kind of self-monitoring and frequent shots of insulin that remains part of the standard treatment plan for Type 1 diabetes today—part of what Bernstein had been pushing for years.

This was only partial vindication for Bernstein. The medical establishment never fully embraced Bernstein or the strict low-carb diet that he prescribed, which some considered unrealistic.

Taubes said that Bernstein was a bit of a “thorny character” who was easy for the establishment to dislike. He also noted that’s something that comes with the territory when you spend your career telling people they’re wrong and you’re right.

“But often it’s the people who are not easy to like,” Taubes said, “who are the ones who are willing to challenge entire establishment belief systems.”

For the full obituary see:

Chris Kornelis. “A Diabetic Who Pioneered Self-Monitoring for Blood Sugar.” The Wall Street Journal (Sat., May 10, 2025): C6.

(Note: the online version of the WSJ obituary has the date May 9, 2025, and has the title “Richard Bernstein, Who Pioneered Diabetics’ Self-Monitoring of Blood Sugar, Dies at 90.”)

Bernstein’s book mentioned above is:

Bernstein, Richard K., MD. Dr. Bernstein’s Diabetes Solution: The Complete Guide to Achieving Normal Blood Sugars. New York: Little, Brown Spark, 2011.

Taubes’s book mentioned above is:

Taubes, Gary. Rethinking Diabetes: What Science Reveals About Diet, Insulin, and Successful Treatments. New York: Knopf, 2024.

Fraudulently Doctored Images and “Suspect Data” in Many Leading Cancer Research Papers

Charles Piller in his Doctored paints a damning picture of doctored images and suspect data rampant in the leading scientific literature on Alzheimer’s disease. Not only were leading scientists guilty of fraud, but the key institutions of scientific research (journals, universities, and government grant-making agencies) failing their oversight duty, and when outsiders stepped in to provide oversight, delayed and minimized their responses. Practicing and turning a blind eye to fraud matters, since Alzheimer’s patients are depending on this research. And researchers who do not commit fraud suffer because they appear to have worse research records than those compiled by the fraudsters. So the honest get worse academic appointments and fewer grants.

After reading Doctored I was depressed, but I at least hoped that this pathology was limited to this one (albeit an important one) area of medical research. But in the article quoted below, evidence is presented that there is substantial similar doctored images and suspect data in the field of cancer research.

A side issue in the quoted article is worth highlighting. In the absence of credible oversight from the institutions tasked with oversight, oversight is being done by competent volunteers, with the aid of A.I. These volunteers do not receive compensation for their work, and in fact are probably pay a price for it, since they alienate powerful scientists and scientific institutions. But if science is a search for truth, and truth matters for cures, they are doing a service to us all, and especially to those who suffer from major diseases such as Alsheimer’s and cancer.

On the connection with the Doctored book, it is worth noting that the article quotes Dr. Matthew Schrag, who is the most important source in Doctored. The article also quoted Elisabeth Bik, who does not have an MD like Schrag but has a PhD in microbiology, and who is another important source in Doctored.

(p. A1) The stomach cancer study was shot through with suspicious data. Identical constellations of cells were said to depict separate experiments on wholly different biological lineages. Photos of tumor-stricken mice, used to show that a drug reduced cancer growth, had been featured in two previous papers describing other treatments.

Problems with the study were severe enough that its publisher, after finding that the paper violated ethics guidelines, formally withdrew it within a few months of its publication in 2021. The study was then wiped from the internet, leaving behind a barren web page that said nothing about the reasons for its removal.

As it turned out, the flawed study was part of a pattern. Since 2008, two of its authors — Dr. Sam S. Yoon, chief of a cancer surgery division at Columbia University’s medical center, and a more junior cancer biologist — have collaborated with a rotating cast of researchers on a combined 26 articles that a British scientific sleuth has publicly flagged for containing suspect data. A medical journal retracted one of them this month after inquiries from The New York Times.

Memorial Sloan Kettering Cancer Center, where Dr. Yoon worked when much of the research was done, is now investigating the studies. Columbia’s medical center declined to comment on specific allegations, saying only that it reviews “any concerns about scientific integrity brought to our attention.”

Dr. Yoon, who has said his research could lead to better cancer treatments, did not answer repeated questions. Attempts to speak to the other researcher, Changhwan Yoon, an associate research scientist at Columbia, were also unsuccessful.

The allegations were aired in recent months in online comments on a science forum and in a blog post by Sholto David, an independent molecular biologist. He has ferreted out problems in a raft of high-profile cancer research, including dozens of papers at a Harvard cancer center that were subsequently referred for retractions or corrections.

From his flat in Wales, Dr. David pores over published images of cells, tumors and mice in his spare (p. A17) time and then reports slip-ups, trying to close the gap between people’s regard for academic research and the sometimes shoddier realities of the profession.

. . .

Armed with A.I.-powered detection tools, scientists and bloggers have recently exposed a growing body of such questionable research, like the faulty papers at Harvard’s Dana-Farber Cancer Institute and studies by Stanford’s president that led to his resignation last year.

But those high-profile cases were merely the tip of the iceberg, experts said. A deeper pool of unreliable research has gone unaddressed for years, shielded in part by powerful scientific publishers driven to put out huge volumes of studies while avoiding the reputational damage of retracting them publicly.

The quiet removal of the 2021 stomach cancer study from Dr. Yoon’s lab, a copy of which was reviewed by The Times, illustrates how that system of scientific publishing has helped enable faulty research, experts said. In some cases, critical medical fields have remained seeded with erroneous studies.

“The journals do the bare minimum,” said Elisabeth Bik, a microbiologist and image expert who described Dr. Yoon’s papers as showing a worrisome pattern of copied or doctored data. “There’s no oversight.”

. . .

Dr. Yoon, a stomach cancer specialist and a proponent of robotic surgery, kept climbing the academic ranks, bringing his junior researcher along with him. In September 2021, around the time the study was published, he joined Columbia, which celebrated his prolific research output in a news release. His work was financed in part by half a million dollars in federal research money that year, adding to a career haul of nearly $5 million in federal funds.

. . .

The researchers’ suspicious publications stretch back 16 years. Over time, relatively minor image copies in papers by Dr. Yoon gave way to more serious discrepancies in studies he collaborated on with Changhwan Yoon, Dr. David said. The pair, who are not related, began publishing articles together around 2013.

But neither their employers nor their publishers seemed to start investigating their work until this past fall, when Dr. David published his initial findings on For Better Science, a blog, and notified Memorial Sloan Kettering, Columbia and the journals. Memorial Sloan Kettering said it began its investigation then.

. . .

A proliferation of medical journals, they said, has helped fuel demand for ever more research articles. But those same journals, many of them operated by multibillion-dollar publishing companies, often respond slowly or do nothing at all once one of those articles is shown to contain copied data. Journals retract papers at a fraction of the rate at which they publish ones with problems.

. . .

“There are examples in this set that raise pretty serious red flags for the possibility of misconduct,” said Dr. Matthew Schrag, a Vanderbilt University neurologist who commented as part of his outside work on research integrity.

. . .

Experts said the handling of the article was symptomatic of a tendency on the part of scientific publishers to obscure reports of lapses.

“This is typical, sweeping-things-under-the-rug kind of nonsense,” said Dr. Ivan Oransky, co-founder of Retraction Watch, which keeps a database of 47,000-plus retracted papers. “This is not good for the scientific record, to put it mildly.”

For the full story, see:

Benjamin Mueller. “Cancer Doctor Is in Spotlight Over Bad Data.” The New York Times. (Fri., February 16, 2024): A1 & A17.

(Note: ellipses added.)

(Note: the online version has the date Feb. 15, 2024 [sic], and has the title “A Columbia Surgeon’s Study Was Pulled. He Kept Publishing Flawed Data.”)

Piller’s book mentioned in my initial comments is:

Piller, Charles. Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s. New York: Atria/One Signal Publishers, 2025.

“A.I.s Are Overly Complicated, Patched-Together Rube Goldberg Machines Full of Ad-Hoc Solutions”

A.I. can be a useful tool for searching and summarizing the current state of consensus knowledge. But I am highly dubious that it will ever be able to make the breakthrough leaps that some humans are sometimes able to make. And I am somewhat dubious that it will ever be able to make the resilient pivots that all of us must sometimes make in the face of new and unexpected challenges.

(p. B2) In a series of recent essays, [Melanie] Mitchell argued that a growing body of work shows that it seems possible models develop gigantic “bags of heuristics,” rather than create more efficient mental models of situations and then reasoning through the tasks at hand. (“Heuristic” is a fancy word for a problem-solving shortcut.)

When Keyon Vafa, an AI researcher at Harvard University, first heard the “bag of heuristics” theory, “I feel like it unlocked something for me,” he says. “This is exactly the thing that we’re trying to describe.”

Vafa’s own research was an effort to see what kind of mental map an AI builds when it’s trained on millions of turn-by-turn directions like what you would see on Google Maps. Vafa and his colleagues used as source material Manhattan’s dense network of streets and avenues.

The result did not look anything like a street map of Manhattan. Close inspection revealed the AI had inferred all kinds of impossible maneuvers—routes that leapt over Central Park, or traveled diagonally for many blocks. Yet the resulting model managed to give usable turn-by-turn directions between any two points in the borough with 99% accuracy.

Even though its topsy-turvy map would drive any motorist mad, the model had essentially learned separate rules for navigating in a multitude of situations, from every possible starting point, Vafa says.

The vast “brains” of AIs, paired with unprecedented processing power, allow them to learn how to solve problems in a messy way which would be impossible for a person.

. . .

. . ., today’s AIs are overly complicated, patched-together Rube Goldberg machines full of ad-hoc solutions for answering our prompts. Understanding that these systems are long lists of cobbled-together rules of thumb could go a long way to explaining why they struggle when they’re asked to do things even a little bit outside their training, says Vafa. When his team blocked just 1% of the virtual Manhattan’s roads, forcing the AI to navigate around detours, its performance plummeted.

This illustrates a big difference between today’s AIs and people, he adds. A person might not be able to recite turn-by-turn directions around New York City with 99% accuracy, but they’d be mentally flexible enough to avoid a bit of roadwork.

For the full commentary see:

Christopher Mims. “We Now Know How AI ‘Thinks.’ It Isn’t Thinking at All.” The Wall Street Journal (Saturday, April 26, 2025): B2.

(Note: ellipses added.)

(Note: the online version of the commentary has the date April 25, 2025, and has the title “We Now Know How AI ‘Thinks’—and It’s Barely Thinking at All.”)

A conference draft of the paper that Vafa co-authored on A.I.’s mental map of Manhattan is:

Vafa, Keyon, Justin Y. Chen, Ashesh Rambachan, Jon Kleinberg, and Sendhil Mullainathan. “Evaluating the World Model Implicit in a Generative Model.” In 38th Conference on Neural Information Processing Systems (NeurIPS). Vancouver, BC, Canada, Dec. 2024.

Director of the N.I.H. Was “Subject to Censorship by the Actions of the Biden Administration”

During the Covid-19 pandemic, I had an invited essay cancelled by the OECD in which I argued for freedom of speech in science, and especially for toleration of a diversity of views during the pandemic. So I have sympathy for the attacks Dr. Bhattacharya suffered during the pandemic and wish him well as the Director of the National Institutes of Health.

(p. B1) Dr. [Jay] Bhattacharya, who has a medical degree and is a professor of medicine but never practiced, burst into the spotlight in October 2020, when he co-wrote an anti-lockdown treatise, the Great Barrington Declaration. It argued for “focused protection” — a strategy to protect the elderly and vulnerable while letting the virus spread among younger, healthier people.

Many scientists countered that walling off at-risk populations from the rest of society was a pipe dream.

The nation’s medical leadership, including Dr. Francis S. Collins, who retired last week, and Dr. Anthony S. Fauci, then director of the National Institute of Allergy and Infectious Diseases, denounced the plan. Referring to Dr. Bhattacharya and his co-authors as “fringe epidemiologists,” Dr. Collins wrote in an email that “there needs to be a quick and devastating takedown of its premises.”

Dr. Bhattacharya told senators on Wednesday [March 5, 2025] that he had been “subject to censorship by the actions of the Biden administration.” Past N.I.H. officials, he said, “oversaw a culture of cover-up, obfuscation and a lack of tolerance for ideas that differ from theirs.”

For the full story see:

Benjamin Mueller and Sheryl Gay Stolberg. “Guarded Nominee for N.I.H. Faces Sharp Questions on Vaccines and Research Cuts.” The New York Times (Thursday, March 6, 2025): A18.

(Note: bracketed date added.)

(Note: the online version of the story has the date March 5, 2025, and has the title “Guarded N.I.H. Nominee Faces Sharp Questions on Vaccines and Research Cuts.”)